The goal of this project is to examine biological and early developmental factors in patterns of substance use in young men from early adolescence to the transition to adulthood. The project builds on an ongoing prospective, longitudinal study of 310 high-risk young men who have been followed since infancy using multiple methods (e.g., observation, interview) and informants (e.g., parents, teachers, peers) and spanning child, family, and extra-familial risk factors. As participants undergo the transition to adulthood and face challenges in interpersonal and instrumental domains, the project will incorporate data on genetics and brain function to understand how these individual differences in underlying, emerging biology factors, separately and in combination, influence patterns of use for drugs, alcohol, and nicotine. Assessments of brain function will examine the contribution of function in mesolimbic and corticolimbic neural circuits at two time points by conducting functional MRI of participants' striatal reactivity to reward stimuli, amygdala reactivity to threat stimuli, resting cerebral blood flow, and resting functional connectivity. The inclusion of fMRI at this point in the longitudinal study will provide detailed information on the association between brain function and genetic factors, early development, social context, and substance use. The guiding hypothesis of the project is that stable characteristics such as a history of antisocial behavior and impulsivity; family and extra- familial contextual risk; brain function; and genetic variants associated with substance use- related brain function will contribute to longitudinal patterns of substance use. In addition, it is expected that the success participants have in establishing stable romantic relationships and employment/educational training during the transition to adulthood will attenuate associations between risk factors and patterns of substance use in early adulthood. The project provides an unprecedented opportunity to examine factors spanning from early childhood through early adulthood that are related to substance use and to link such data with data on genes and brain function during the transition from adolescence to adulthood using a low-income sample of ethnically diverse males at high risk for maladaptive adult functioning. Thus, the study offers the potential to advance our understanding of pathways to substance use problems and guide developmentally informed prevention and intervention efforts. PUBLIC HEALTH RELEVANCE: The goal of this project is to examine biological and early developmental factors in patterns of substance use in young men from early adolescence to the transition to adulthood. The project builds on an ongoing prospective, longitudinal study of 310 high-risk young men who have been followed since infancy using multiple methods and informants, and spanning child, family, and extra-familial risk factors. These data will be linked with data on genes and brain function during the transition from adolescence to adulthood. Thus, the study offers the potential to advance our understanding of pathways to substance use problems and guide developmentally informed prevention and intervention efforts.